Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

IPT [N-(3-iodopropen-2-yl)- 2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane] is a new cocaine analogue which allows the presynaptic dopamine transporters to be imaged with single-photon emission tomography (SPET) as early as 1-2 h post injection. In the present study [123I]IPT SPET was performed in patients with Parkinson's disease (PD) to analyse the relationship between specific dopamine tansporter binding and clinical features of the disease. Twenty-six PD patients (Hoehn and Yahr stages I-IV, age range 40-79 years) and eight age-matched controls were studied. SPET imaging was performed 90-120 min after injection of 160-185 MBq [123I]IPT using a triple-head camera. For semiquantitative evaluation of specific [123I]IPT binding, ratios between caudate, putamen and background regions were calculated. Specific [123I]IPT uptake was significantly reduced in PD patients compared to controls. Most patients showed a marked asymmetry with a more pronounced decrease in [123I]IPT binding on the side contralateral to the predominant clinical findings. The putamen was always more affected than the caudate. [123I]IPT binding was significantly correlated with disease duration (r=-0.7, P<0.0001) but not with the age of PD patients (r=-0.10, P=0. 61). Specific [123I]IPT uptake in the caudate and putamen, and putamen to caudate ratios, decreased with increasing Hoehn and Yahr stage. Our findings indicate that [123I]IPT SPET may be a useful technique to estimate the extent of nigrostriatal degeneration in PD patients. Close relationships between striatal [123I]IPT binding and clinical features of the disease suggest that this method can be used to objectively follow the course and progression of PD. The reduced putamen to caudate ratios observed even in patients with mild, newly recognized symptoms indicate that particularly this parameter may help to establish the correct diagnosis in the early course of PD.
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PMID:Relationship between clinical features of Parkinson's disease and presynaptic dopamine transporter binding assessed with [123I]IPT and single-photon emission tomography. 909 93

We investigated the availability of dopamine reuptake sites in the striata of two patients with productive symptoms and neuroleptic therapy as well as progressive parkinsonism using the new dopamine transporter ligand [123I]N-(3-iodopropen-2-yl)-2beta-carbo-methoxy-3beta- (4-chlorophenyl)tropane (IPT) and single photon emission computed tomography (SPECT). Normal specific binding in the caudate nucleus was 8.6 +/- 1.2 and in the putamen 6.5 +/- 1.3 (mean +/- S.D.; n = 8; mean age, 56.7 years; range 41-67 years). Patient 1 (age 43) was admitted to our clinic at age 38 because of left-sided parkinsonism. At age 40, she developed paranoid psychosis without change after cessation of L-DOPA and lisuride treatment for 3 months. She was diagnosed as a schizophrenic, paranoid subtype (DSM-III-R). IPT-SPECT showed a loss of dopaminergic nerve terminals (right caudate/putamen, 5.16/2.0; left caudate/putamen, 5.92/2.66). Patient 2 (age, 61 years) had a history of paranoid psychosis for approx. 30 years. He experienced progressive right-sided parkinsonism since age 57 when treated with clozapine. IPT-SPECT showed a marked reduction of striatal dopamine transporter binding (right caudate/putamen, 5.06/1.65; left caudate/putamen, 3.8/1.12). Our findings indicate that patients may suffer contemporaneously from Parkinson's disease and schizophrenia. In these patients, the proof of a nigrostriatal dopaminergic deficit justifies treatment with neuroleptics and dopaminergic drugs. Imaging of dopamine transporters with SPECT and IPT or a related compound represents an attractive alternative to the more complex measurements of fluorodopa uptake with positron emission tomography (PET).
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PMID:Reduced striatal dopaminergic innervation shown by IPT and SPECT in patients under neuroleptic treatment: need for levodopa therapy? 975 2

Rapid eye movement (REM) sleep behaviour disorder (RBD) is characterized by complex behaviour during REM sleep. The aetiology of this disorder is still unknown, but a recent study showed an association between RBD and Parkinson's disease. We therefore studied striatal postsynaptic dopamine D2 receptor density with [123I](S)-2-hydroxy-3-iodo-6-methoxy-(1-ethyl-2-pyrrolidinylmethyl ) benzamide ([123I]IBZM) and the striatal presynaptic dopamine transporter with (N)-(3-iodopropene-2-yl)-2beta-carbomethoxy-3beta-(4-chlorop henyl) tropane ([123I]IPT) using single-photon emission computed tomography (SPECT) in patients with idiopathic RBD. We compared the [123I]IPT-SPECT results of five patients with polysomnographically confirmed idiopathic RBD with the [123I]IPT-SPECTs of seven age- and sex-matched controls without a history of sleep disorders, and of 14 patients with Parkinson's disease (Hoehn and Yahr stage I). All RBD patients had significantly reduced striatal [123I]IPT binding compared with the controls (RBD: right, 2.94 +/- 0.32, left, 3.03 +/- 0.41; controls: right, 4.41 +/- 0.17, left, 4.34 +/- 0.21; P = 0.003), but significantly higher striatal [123I]IPT binding compared with the striatum contralateral to the symptomatic body side of the Parkinson's disease patients (Parkinson's disease: ipsilateral, 3.17 +/- 0.36, P = 0.298; contralateral, 2.51 +/- 0.31, P = 0.019). Uptake of [123I]IBZM was not significantly different in the RBD group compared with the controls. This study demonstrates that [123I]IPT-SPECT is a useful diagnostic tool in RBD and that reduced striatal dopamine transporters may be a pathophysiological mechanism of idiopathic RBD. (Results are given as mean +/- standard deviation.)
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PMID:Reduced striatal dopamine transporters in idiopathic rapid eye movement sleep behaviour disorder. Comparison with Parkinson's disease and controls. 1082 54

Imaging of striatal dopamine transporter binding allows differentiation between patients with Parkinson's disease and controls. We investigated the use of this technique to monitor disease progression. We used N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(4-chlorophenyl) tropane (IPT) and single photon emission computed tomography (SPECT) to determine dopamine transporter function in eight patients with Parkinson's disease Hoehn and Yahr stage I to III over time. Patients were recruited from the movement disorder clinic and were studied at entry and after a follow-up period of 1 and 2 years. Specific striatal IPT binding was measured with a manual region of interest technique. At entry, all patients showed a reduction of striatal IPT uptake of approximately 50% compared to controls, with a mean striatum to background ratio of 3.61 +/- 0.72 (controls, 7.34 +/- 1.18). Putamen to background ratios were initially measured as 2.42 +/- 0.74 and caudate to background ratios as 5.00 +/- 0.73 (controls, 6.46 +/- 1.22 for putamen and 8.58 +/- 1.36 for caudate). Specific striatal IPT binding decreased by a mean of 6.6% in the first year and another 5.3% in the second year. Changes of specific IPT binding over time were similar in caudate and putamen. In patients with clinically asymmetric disease, differences between the rate of decline in the ipsilateral and contralateral sides could not be detected. The findings suggest that IPT SPECT can quantify the reduction of dopamine transporter binding over time. This technique seems to be a useful tool in monitoring the intra-individual progression of dopaminergic cell loss in patients with Parkinson's disease and may help to follow the effects of putative neuroprotective drugs in future clinical trials.
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PMID:Striatal dopamine transporter binding in early to moderately advanced Parkinson's disease: monitoring of disease progression over 2 years. 1140 85

Functional imaging of the dopamine transporter (DAT) defines integrity of the dopaminergic system and has its main clinical application in patients with mild, incomplete, or uncertain parkinsonism. Imaging with specific single positron emission computerised tomography ligands for DAT (FP-CIT, beta-CIT, IPT, TRODAT) provides a marker for presynaptic neuronal degeneration. Striatal uptake correlates with disease severity, in particular bradykinesia and rigidity, and monitoring of progression assists in clinical trials of potential neuroprotective drugs. DAT imaging is abnormal in idiopathic Parkinson's disease, multiple system atrophy and progressive supranuclear palsy and does not distinguish between these disorders. Dopamine loss is seen even in the earliest clinical presentations of true parkinsonism; a normal scan suggests an alternative diagnosis such as essential tremor, vascular parkinsonism (unless there is focal basal ganglia infarction), drug-induced parkinsonism, or psychogenic parkinsonism. Congruence between working clinical diagnosis and DAT imaging increases over time in favour of baseline DAT imaging results. Additional applications are characterising dementia with parkinsonian features (abnormal results in dementia with Lewy bodies, normal in Alzheimer's disease); and differentiating juvenile-onset Parkinson's disease (abnormal DAT) from dopa-responsive dystonia (normal DAT).
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PMID:Role of dopamine transporter imaging in routine clinical practice. 1546

Hereditary progressive dystonia with marked diurnal fluctuation/dopa-responsive dystonia (HPD/DRD) shows the considerable heterogeneity of clinical phenotypic expression and a dramatic sustained response to levodopa. The autosomal dominant HPD/DRD is caused by mutations in the gene coding GTP cyclohydrolase I (GCH I), the enzyme that catalyzes the first step in the biosynthesis of tetrahydrobiopterin. Previous studies suggested that normal [18F]Dopa positron emission tomography or [123I]beta-CIT single-photon emission computed tomography (SPECT) imaging, indicating intact structural integrity of nigrostriatal neurons, may be useful for differentiating HPD/DRD from clinically similar conditions such as juvenile Parkinson's disease with dystonia that have a considerably poorer prognosis. We here report a Korean family affected with HPD/DRD due to a novel missense mutation of the GCH I gene (T-->G mutation in exon 2), Met 137 Arg, which may change the conformation of the binding site of GCH I. The clinical features are considerably variable within the family. We documented normal striatal uptake of [123I]IPT, a dopamine transporter ligand with fast washout kinetics, in our patients by using SPECT. This method can be helpful in diagnosing HPD/DRD in uncertain cases.
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PMID:A novel missense mutation of the GTP cyclohydrolase I gene in a Korean family with hereditary progressive dystonia/dopa-responsive dystonia. 1516 67

Putative neurotoxic actions of levodopa and neuroprotective effects of dopamine agonists, as indicated by laboratory and animal studies, provide the rationale to study their effect on the progression of Parkinson's disease. Aim of this pilot study was to compare the effects of monotherapy with the dopamine agonist alpha-dihydroergocryptine (DEC) versus monotherapy with levodopa on nigrostriatal dopaminergic neurons as measured with dopamine transporter (DAT) SPECT. 25 PD patients (H&Y stages 1 to 2.5) entered this study and were treated in a randomized fashion either with DEC (101+/-39 mg) or levodopa (369+/-51 mg) monotherapy. 16/25 patients (8 per group) terminated the study after 52 weeks. In each patient SPECT investigations with [123I]IPT were performed at baseline and after 52 weeks to assess changes of specific DAT binding over time. Changes in clinical symptoms were assessed by UPDRS score. The mean annual decline rate in striatal IPT-binding was lower in the DEC group (8.4%) compared to the levodopa group (10.4%). The difference was most accentuated in the putamen (DEC: 7.3%; levodopa: 16.2%; p = 0.16). Due to the small sample size and the relatively short observation period, however, group differences did not reach a statistical significant level. The results of this pilot study suggest that as compared to levodopa monotherapy DEC may have beneficial effects on decline of dopamine transporter binding similar to those recently described for pramipexole.
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PMID:Comparison of alpha-dihydroergocryptine and levodopa monotherapy in Parkinson's disease: assessment of changes in DAT binding with [123I]IPT SPECT. 1525 92

The cause of restless legs syndrome (RLS) is unknown, but an involvement of the dopaminergic system and a possible relation to Parkinson's disease (PD) is suggested by the positive response to dopaminergic treatment. We imaged the striatal dopamine transporter with [(123)I] N-(3-iodopropen-2-yl)-2beta-carbomethoxy-3beta-(chloro-phenyl) tropane ([(123)I]IPT) and single-photon emission computed tomography (SPECT) in 28 RLS patients, and compared the results with transporter binding in 29 patients with early PD and 23 age-matched controls. No difference in IPT binding was found between RLS patients and controls. IPT binding was correlated significantly with age in RLS patients and controls, whereas there was no relation with the duration of symptoms or severity of RLS. PD patients presented significant lower presynaptic IPT binding ipsi- and contralateral to the affected body side compared with RLS patients or controls. We found no common characteristics between RLS patients and patients with early PD detectable by dopamine transporter SPECT. Our results do not strengthen an identical pathophysiologic pathway between RLS and PD on the level of nigrostriatal presynaptic terminal function.
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PMID:Presynaptic dopaminergic function in patients with restless legs syndrome: are there common features with early Parkinson's disease? 1539 76

This study evaluated the striatal specific binding ratio (SBR), the anterior to posterior ratio of the striatum (APR) and its reproducibility by employing a template-based registration (TBR) method using the coregistered to the standard T1 magnetic resonance (MR) template (SMRT) as a replacement for the MR image of each patient. The 123I-IPT single photon emission computed tomography (SPECT) images of 30 patients with Idiopathic Parkinson's disease (IPD) and 11 normal controls were analyzed. The region of interest (ROI) was positioned manually in the same slice showing the highest striatal activity using the manual ROI method, while the ROI were positioned automatically in the mid striatal slice of the SPECT image coregistered to the SMRT. The SBR obtained using the TBR method showed a strong correlation with those using the manual method in all groups: normal controls (r = 0.851, P = 0.001), early IPD (r = 0.841, P < 0.001), and severe IPD (r = 0.702, P = 0.007). The APR obtained by the TBR correlated with those using the manual method in only the early IPD (r = 0.72, P = 0.001), while those obtained using the manual method showed no correlation in the three groups (P > 0.05). The reproducibility (rmsCV) of the TBR method was 7.2% (normal controls, 5.2%; mild IPD, 4.2%; severe IPD, 10.8%), while the reproducibility of the manual method was 31% (normal controls, 19.7%; mild IPD, 21.7%; severe IPD, 46.2%). This shows that the use of 123I-IPT SPECT for assessing IPD is affected by the method used to position the striatal ROI. This study showed that the TBR method using the SMRT is useful in diagnosing the IPD and assessing the disease severity with a high reproducibility, indicating a possibility of using the TBR method as a good replacement for the manual method.
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PMID:Quantification analysis of 123I-IPT single photon emission computed tomography uptake in the striatum of parkinsonism with the standard magnetic resonance template. 1647 55

We evaluated the patterns of dopamine transporter loss in the striatum of ten controls, twenty patients with Parkinson's disease (PD), and nine with progressive supranuclear palsy (PSP) using (123)I-IPT single photon emission tomography (SPECT). Four ROIs in the striatum correspond to the head of caudate nucleus (ROI 1), a transitional region between head of caudate and putamen (ROI 2), anterior putamen (ROI 3), and posterior putamen (ROI 4). A striatal ratio of specific to nondisplaceable uptake (V3'') was calculated normalizing the activity of the ROIs to that of occipital cortex. V3'' values were significantly reduced in all ROIs of PD and PSP patients, compared with controls (p=0.001). V3'' value in ROI 2 was significantly lower in PSP group, compared with PD group (p=0.02). The percent reductions of striatal uptake in ROI 1, ROI 2, ROI 3 and ROI 4 were 56%, 53%, 64% and 78% in PD patients, whereas 75%, 72%, 75% and 77% in PSP patients, respectively. The reduction patterns of uptake were significantly different between PD and PSP groups (p=0.001). In PD patients, the percent reductions of (123)I-IPT uptake were significantly greater in ROI 3 and 4 compared with ROI 1 or 2, whereas those were similar in all ROIs of PSP patients. In addition, PD patients showed a significantly higher posterior putamen/caudate ratio of reduced (123)I-IPT uptake than the anterior putamen/caudate ratio (p=0.005). Our results implicate that (123)I-IPT SPECT is a relatively simple and reliable technique that may be useful in differentiating PD from PSP.
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PMID:Differential patterns of dopamine transporter loss in the basal ganglia of progressive supranuclear palsy and Parkinson's disease: analysis with [(123)I]IPT single photon emission computed tomography. 1647 71


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